How the brain learns from mistakes

University of Basel scientists have identified a protein that plays a major role in forming the right kind of connections in the rapidly growing brain of newborn mammals.

The protein was found to help neuronal cells in the brain repair errors when they had connected to the wrong type of cell and it may shed light on why some young children go on to develop disorders such as autism and schizophrenia, said the researchers.

Peter Scheiffele and team at the Biozentrum of the University of Basel have been able to document this phenomenon using advanced microscopy techniques in the developing cerebellum, a brain area required for fine movement control.

They discovered that a protein traditionally associated with bone development is responsible for correcting errors while neurons connect to their correct partners in the cerebellum.

In the study, Scheiffele's group demonstrated that these mossy fiber inputs often connect with Purkinje neurons during early brain development, in addition to granule cells. These incorrect Purkinje connections are then subsequently eliminated within a week, establishing proper specificity in the cerebellum.

They also found that Bone morphogenetic protein 4 (BMP4) helps correct these initial errors. Originally, BMP4 was linked with the specialization of cells during osteogenesis.

"If inappropriate connections between neurons are not subsequently eliminated, this can lead to substantial disturbances in the brain. Autism could also be linked to this form of failure to correct errors," explained Scheiffele.

The research group used a genetic mouse model to make their observations. With the help of a fluorescent protein, the different nerve connections could be stained and made visible by an advanced imaging technique that combines light microscopy with electron microscopy.

This allowed multiple types of changes in connectivity to be traced. "These processes can be applied to the development of the human brain and could play an important role in further brain research," added Scheiffele.

The brain undergoes drastic changes during its early life. While the neuronal connections in the brain of a newborn are still relatively unspecific, the selectivity of the synapses steadily increases.